Novel Vaccines to Human Rabies

Abstract

Rabies, the most fatal of all infectious diseases, remains a major public health problem in developing countries, claiming the lives of an estimated 55,000 people each year. Most fatal rabies cases, with more than half of them in children, result from dog bites and occur among low-income families in Southeast Asia and Africa. Safe and efficacious vaccines are available to prevent rabies. However, they have to be given repeatedly, three times for pre-exposure vaccination and four to five times for post-exposure prophylaxis (PEP). In cases of severe exposure, a regimen of vaccine combined with a rabies immunoglobulin (RIG) preparation is required. The high incidence of fatal rabies is linked to a lack of knowledge on the appropriate treatment of bite wounds, lack of access to costly PEP, and failure to follow up with repeat immunizations. New, more immunogenic but less costly rabies virus vaccines are needed to reduce the toll of rabies on human lives. A preventative vaccine used for the immunization of children, especially those in high incidence countries, would be expected to lower fatality rates. Such a vaccine would have to be inexpensive, safe, and provide sustained protection, preferably after a single dose. Novel regimens are also needed for PEP to reduce the need for the already scarce and costly RIG and to reduce the number of vaccine doses to one or two. In this review, the pipeline of new rabies vaccines that are in pre-clinical testing is provided and an opinion on those that might be best suited as potential replacements for the currently used vaccines is offered.

A New Rabies Vaccine Based on a Recombinant Orf Virus (Parapoxvirus) Expressing the Rabies Virus Glycoprotein

“…Since the recent introduction of "reverse genetics" technology (12,13), new live attenuated RABV can be designed, for instance, by gene mutations (see reference 14), duplication or triplication of the RabG gene (15,16), or simultaneous expression of inserted cytokine genes to stimulate the innate immune response (17,18). Some of them are promising candidates of rabies vaccines due to their apathogenicity and improved immunogenicity in animal models.…”

“…Various recombinant rabies vaccines have been generated using different viral vector systems, such as Newcastle disease virus (22), Sindbis virus (23), herpesvirus (24), adenovirus (for a review, see reference 14), or baculovirus (25). Moreover, numerous poxvirus-vectored vaccines expressing RabG have been constructed, as reviewed recently (26).…”

Zoonotic and Animal Vector Mediated Encephalitides

“…With the advent of more sophisticated molecular technologies and a greater understanding of these diseases and their genetic codes, novel vaccines could be developed to help curb or prevent future infections (Seshadri et al, 2003;Diamond & Mehlhop, 2008;Ertl, 2009). As genomes become available, a further characterization of phylogenetic relationships can be made (Mavarez et al, 2002;Bourhy et al, 2005;Jackson et al, 2010).…”

Cloning and Expression of Rabies Virus Glycoprotein Gene into Eukaryotic System

“…The importance of Rabies vaccination is well recognized (13). DNA vaccination technology has grown very fast since 1990s.…”